Daniel Brotman, MD, received his medical degree from the University of Virginia School of Medicine in 1997 and completed a residency in Internal Medicine at Johns Hopkins Hospital in 2000. He spent 5 years as a Hospitalist at the Cleveland Clinic Foundation, where he directed the Hospital Medicine Fellowship Program and was actively involved in research in perioperative medicine as well as cardiovascular complications of hospitalization. Dr. Brotman returned to Johns Hopkins in 2005 to direct the Hospitalist Program and has remained clinically active in Hospital Medicine and inpatient consultative medicine. He currently has external research funding to study hospitalized patients with congestive heart failure, and continues his research in perioperative medicine and vascular disease. Dr. Brotman is a sought-after peer reviewer for over 20 major medical journals, is an Assistant Editor of the Journal of Hospital Medicine, an Associate Editor of the Cleveland Clinic Journal of Medicine and an Editorial Consultant for The Lancet. He is also a member of the Annual Meeting Committee and the Academic Task Force of the Society of Hospital Medicine.

Majid Fotuhi, MD, PhD, is Director of the Center for Memory and Brain Health at Sinai Hospital and an assistant professor of neurology at Johns Hopkins Medical Institutions. He also lectures at the Harvard Medical School. He graduated cum laude from the Harvard-MIT division of Health Sciences and Technology in Boston, where he received his MD, and completed his PhD in neuroscience and neurology residency training at Johns Hopkins Medical Institutions in Baltimore. Dr. Fotuhi has numerous publications and awards for his work in neurobiology, including a teaching award from the American Academy of Neurology.

History

A 65-year-old man presented to the emergency department in April 1999 for evaluation of possible seizures.(1) He had a history of treated hypertension and treated syphilis, and he was undergoing outpatient evaluation for an aortic arch aneurysm. His chief complaint was uncontrollable shaking of his left arm and leg. The first shaking episode had occurred 1 year earlier. At that time, he was walking when he suddenly developed uncontrollable shaking of the left arm and leg. This episode lasted for a few seconds and terminated spontaneously when the patient sat down. From that point onwards, the episodes occurred intermittently, about once or twice a week. The shaking would occur only when the patient was upright and always resolved when he sat or lay down.

He did not seek medical attention for these symptoms because he did not perceive them to represent a serious medical problem. However, during the month before admission the episodes had increased dramatically in frequency – they were occurring many times a day and had caused several falls. By the time of presentation, the patient was unable to walk and complained that every time he stood he would develop the shaking movements. The shaking would abate within seconds when he sat down, such that the duration of each episode was no more than 10 seconds. The character of the episodes was always the same: only the left arm and leg were affected, he always remained alert despite his inability to control the shaking, and he noted no weakness or paresthesias after episodes. He denied any history of seizures, stroke or syncope. He also denied headaches, fever, chest pain, arthralgias and skin rashes.

Examination and investigations

The patient appeared healthy and comfortable. Upper extremity blood pressures were 162/54 mmHg on the left and 73/56 mmHg on the right. He was afebrile. Carotid and radial pulses were graded as 3+ on the left and 1+ on the right. Heart sounds were normal; there was an ejection murmur that radiated to the left carotid artery but not to the right. The lungs were clear, the neck veins were flat and there was no edema. There were no swollen joints or skin rashes. Neurological examination was normal while the patient was sitting or lying down. However, on each attempt to stand up, he developed large-amplitude 3–4 Hz shaking of his left arm and leg. He could not voluntarily control the shaking, yet he remained alert and conversant during each episode. He could not stand upright long enough for orthostatic measurements of blood pressure and pulse.

Brain magnetic resonance imaging (MRI) and magnetic resonance angiography were normal except for mild small vessel ischemic changes. An aortic angiogram (Fig. 25.1) revealed a proximal 5 cm aneurysm of the aorta involving the origin of the innominate artery and obstructing its antegrade flow. However, there was flow in the right subclavian artery via retrograde passage from the right common carotid artery. Circulation in the left common carotid and left subclavian was normal. The right vertebral artery was not visualized.

Several hours after the aortic angiography, the patient developed weakness and numbness in his left arm and leg that were no longer postural but constant. A repeat diffusion-weighted brain MRI scan showed a new small infarct involving the right ventrolateral thalamus and posterior internal capsule (Fig. 25.2).

Diagnosis

Orthostatic limb-shaking transient ischemic attacks (TIAs).

Treatment and outcome

Because immediate cardiac surgery would risk hemorrhagic transformation of this patient’s acute ischemic cerebrovascular accident (CVA), he was observed for a month before he underwent successful graft replacement of the aortic arch and great vessels. Examination of the pathological specimen revealed atherosclerotic changes and mild lymphocytic infiltration of the aortic wall, consistent with (but not specific for) treated syphilitic aortitis. Fortunately, his neurological deficits resolved almost completely with rehabilitation. The patient was last seen in April 2000, and at that time was ambulatory and without weakness or limb-shaking episodes.

Commentary

The patient’s CVA led to symptoms in the same body distribution that had been involved in his preceding limb shaking episodes, indicating that the shaking probably represented recurrent TIAs.(1) Other authors have described limb shaking TIAs caused by internal carotid stenosis, sometimes postural and sometimes preceding ischemic CVAs.(2-4) This case demonstrates that such symptoms can also result from more proximal occlusions.

Although the pathogenesis of limb-shaking TIAs is not well understood, Baumgartner and Baumgartner studied cerebral vasomotor reactivity in a series of patients with this disorder.2 They found that vasodilatation induced by carbon dioxide was absent in the cerebral vessels of the affected hemisphere, implying that the resistance vessels were already maximally dilated. This suggests that the presence of critical ischemia with limited collateralization may predispose to limb-shaking episodes in affected patients. These and other authors have found no evidence of seizure activity on EEG in patients affected by limb-shaking TIAs.(2,3,5,6)

Other explanations of this patient’s symptoms could include focal seizures,7 orthostatic tremor or pure neurosyphilis. Although no EEG was performed during a limb-shaking episode, focal motor seizures were unlikely because of the predictable onset and termination of limb-shaking with standing and sitting. Orthostatic tremor is unlikely because it typically involves both legs and has a higher frequency (13–18 Hz).(8) Neurosyphilis may have triggered inflammatory changes in the cerebral arteries, but is unlikely to have caused the CVA because it occurred shortly after angiography.

What did we learn from this case?

This case illustrates three important clinical points:

TIAs may mimic seizures by presenting with shaking of the extremities;

limb-shaking TIAs, like other TIAs, may signal an impending CVA and should be evaluated thoroughly; and

postural limb-shaking is suggestive of severe impairment of the anterior cerebral circulation and should trigger evaluation of the carotid arteries as well as the proximal aorta if a patient has a history of syphilis or other risk factors for an aortic aneurysm.

How did this case alter our approach to the care and treatment of our epilepsy patients?

We now think of the possibility of limb-shaking TIAs in patients who are thought to have focal motor seizures when the movements are related to posture.

Figure 25.1: Aortic angiogram showing a proximal 5 cm aneurysm of the aorta (Ao) involving the origin of the innominate artery (In) and obstructing its antegrade flow (arrow). However, there is flow in the right subclavian artery (RSC) via retrograde passage from the right common carotid artery (RCC). Circulation in the left common carotid (LCC) and left subclavian (LSC) is normal. The right vertebral artery is not visualized.